The 27-year-old Loupe, who has three top-10 finishes this season, shot 31 on the front nine. Wheatcroft did his work on the four par 5s, playing them in 6 under with two eagles and two birdies.
"Kind of felt like I was trying to keep up the whole time with Steve," Loupe said. "We both had it rolling early. Just solid golf for the most part, just looking to keep that momentum going."
India's Anirban Lahiri was a shot back after a 66.
Phil Mickelson, who has finished in the top five six times in 12 starts at the Wells Fargo Championship but never won, opened with a 69.
"I have been able to play well here over the years, but just haven't been able to break through and get a victory," Mickelson said. "But I will keep knocking on the door and hopefully keep giving myself a chance."
Jim Furyk shot a 73 in his return from an eight-month layoff because of a wrist injury.
Furyk had "no pain, no apprehension," but said he wasn't planning to hit many practice balls after the round -- which didn't exactly upset him.
"I don't enjoy hitting balls, so actually it's kind of fun," Furyk said. "I'm not really allowed to or can't, so I'm enjoying that part of it."